What is the recommended treatment for a neonate presenting with fever?

From the Guidelines

The recommended treatment for a neonate with fever (temperature ≥38°C or 100.4°F) requires immediate medical attention and hospitalization for a full sepsis evaluation. Initial management includes obtaining blood, urine, and cerebrospinal fluid cultures, followed by prompt administration of empiric broad-spectrum antibiotics, typically ampicillin (100-200 mg/kg/day divided every 6 hours) and gentamicin (4-5 mg/kg/day) or a third-generation cephalosporin like cefotaxime (150-200 mg/kg/day divided every 6-8 hours) 1. These antibiotics cover common neonatal pathogens including Group B Streptococcus, Escherichia coli, and Listeria monocytogenes. Supportive care with IV fluids, temperature management, and close monitoring of vital signs is essential. Antibiotic therapy typically continues for 7-14 days depending on culture results and clinical response. The aggressive approach is necessary because neonates have immature immune systems and can rapidly deteriorate from infections. They often present with subtle signs, and fever may be the only indication of a serious bacterial infection that could lead to sepsis, meningitis, or death if not promptly treated.

Key Considerations

• The risk of serious bacterial infection (SBI) in neonates with fever is significant, with a reported risk of 13% in neonates aged 3 to 28 days 1.
• The definition of fever varies between studies, but a rectal temperature of greater than or equal to 38.0 C (100.4 F) is commonly used 1.
• The management of febrile neonates requires a thorough evaluation, including blood, urine, and cerebrospinal fluid cultures, to identify the source of infection.
• Empiric broad-spectrum antibiotics are recommended to cover common neonatal pathogens, including Group B Streptococcus, Escherichia coli, and Listeria monocytogenes.

Treatment Approach

• Prompt administration of empiric broad-spectrum antibiotics is crucial to prevent complications and improve outcomes in neonates with fever.
• Supportive care, including IV fluids, temperature management, and close monitoring of vital signs, is essential to manage the neonate's condition.
• Antibiotic therapy should be tailored based on culture results and clinical response, with a typical duration of 7-14 days.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Injection, USP and other antibacterial drugs, Gentamicin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria Clinical studies have shown gentamicin injection to be effective in bacterial neonatal sepsis; bacterial septicemia and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns) In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

The recommended treatment for a neonate presenting with fever may include gentamicin as part of the treatment regimen, possibly in combination with a penicillin-type drug, for suspected bacterial sepsis or staphylococcal pneumonia 2.

• Gentamicin has been shown to be effective in bacterial neonatal sepsis.
• A penicillin-type drug, such as ampicillin, may also be used as concomitant therapy with gentamicin 3.
• The treatment should be guided by bacterial culture and susceptibility results, and the decision to continue therapy should be based on these results, as well as the severity of the infection.

From the Research

Neonate Fever Treatment

The recommended treatment for a neonate presenting with fever is a topic of ongoing research and debate.

• The use of ampicillin and gentamicin has been shown to be effective in preventing neonatal sepsis and other infections 4, 5.
• A study published in 2011 found that the combination of ampicillin and gentamicin provided appropriate antibiotic coverage for febrile infants aged ≤ 90 days 5.
• Another study published in 2023 suggested that short-course empiric antibiotic therapy for possible early-onset sepsis in the NICU may be safe and effective 6.
• The management of febrile neonates in US pediatric emergency departments has been found to vary widely, with some hospitals using more aggressive treatment approaches than others 7.
• The use of inflammatory markers such as C-reactive protein and procalcitonin has been studied as a tool for risk stratification in febrile infants, but their diagnostic accuracy is limited 8.

Antibiotic Treatment

• The traditional combination of ampicillin and gentamicin is still considered appropriate for empirical treatment of febrile infants aged ≤ 90 days 5.
• A study published in 2025 found that ampicillin and gentamicin treatment was associated with lower rates of clinical chorioamnionitis, maternal postpartum complications, and neonatal adverse outcomes 4.
• The duration of antibiotic therapy for suspected early-onset sepsis may be safely discontinued within 24 hours 6.

Risk Stratification

• The use of viral testing and inflammatory markers such as procalcitonin can help better stratify young febrile infants at risk for invasive bacterial infections 8.
• Infants who are deemed low risk may benefit from shorter observation times and tailored or discontinued antibiotic therapy 8.